The bacterium Bordetella pertussis elaborates a toxin (pertussis toxin) which produces symptoms of whoop pertussis, generally known as whooping cough. In the U.S., this disease affected over 200,000 children a year prior to the initial development of a whole-cell pertussis vaccine, killing as many as 12,000 per year. Since the introduction of this whole-cell vaccine, consisting of formalin- and/or heat-treated B. pertussis, the incidence of the disease has declined dramatically. However, the whole-cell vaccine can cause severe adverse reactions, including occasional permanent neurological damage.
In order to minimize such adverse reactions, an acellular vaccine has been developed containing purified pertussis toxin treated with formalin. Studies have indicated that for either the whole-cell or the acellular vaccine the attack rate, that is, the percent of children exposed to the disease who actually develop symptoms is from 10 to 15% while the attack rate in non-immunized children is 83%. Thus, both vaccines provide similar inadequate protection. The variable protection afforded by existing vaccines suggests either variable characteristics of, or responses to, the immunizing material and may be due to the fact that the effect of traditional techniques previously used for the inactivation of pertussis toxin are uncertain. For example, the toxin may be temporarily inactivated by heat or formalin treatment, only to have the denatured portions restructure to form either active or modified toxins which produce pertussis symptoms or neurologic damage.
Pertussis toxin is an oligomeric protein consisting of an A-protomer, containing an enzymatically active (catalytic) subunit, referred to as the S.sub.1 subunit; linked to a B-oligomer which consists of one S.sub.2, one S.sub.3, two S.sub.4 and one S.sub.5 subunits. The B-oligomer binds to target cells, delivering the S.sub.1 subunit which then produces symptoms of pertussis by ADP-ribosylating specific guanine-nucleotide-binding proteins and disrupting cellular functions.